Natural Product: NPC138245

Natural Product IDNPC138245
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Rabdoinflexin B
IUPAC Name n.a.
Synonyms Rabdoinflexin B
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL550840
PubChem CID 14466855
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids
          • [CHEMONTID:0003782] Kaurane diterpenoids

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey CUJHFFISDMEILV-PIBILOFFSA-N
Standard InCHI InChI=1S/C20H30O5/c1-9-10-7-11(21)15-19(4)12(18(2,3)6-5-13(19)22)8-14(23)20(15,16(9)24)17(10)25/h10-15,17,21-23,25H,1,5-8H2,2-4H3/t10-,11-,12+,13-,14+,15-,17+,19-,20+/m0/s1
SMILES C=C1[C@@H]2C[C@@H]([C@H]3[C@@]4(C)[C@H](C[C@H]([C@@]3(C1=O)[C@@H]2O)O)C(C)(C)CC[C@@H]4O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   350.21 Volume:   358.929
?
Van der Waals volume.
Dense:   0.976 LogP:   1.248
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.645
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.423
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   21.0
TPSA:   97.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   4.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.489 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.164 Fsp3:   0.85
MCE-18:   112.703
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.395 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.051
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.332 Promiscuous compounds:   0.131

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.475 MDCK Permeability:   -5.094
Pgp-inhibitor:   0.112 Pgp-substrate:   0.743
PAMPA:   0.997
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.748
20% Bioavailability (F20%):   0.938 30% Bioavailability (F30%):   0.96
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.665
Plasma Protein Binding (PPB):   42.933% Volume Distribution (VD):   -0.135
Fu: 57.982%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.981 BCRP inhibitor:   0.046
BSEP inhibitor:   0.863

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.004
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.005
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.372
CYP2D6-inhibitor:   0.088 CYP2D6-substrate:   0.006
CYP3A4-inhibitor:   0.009 CYP3A4-substrate:   0.024
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.036
HLM stability:   0.072
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  6.243 Half-life (T1/2):  2.836

ADMET: Toxicity

hERG Blockers:  0.02 hERG Blockers (10um):  0.122
Human Hepatotoxicity (H-HT):  0.785 Drug-induced Liver Injury (DILI):  0.832
AMES Toxicity:  0.673 Rat Oral Acute Toxicity:  0.467
Maximum Recommended Daily Dose:  0.828 Skin Sensitization:  0.962
Carcinogencity:  0.789 Eye Corrosion:  0.002
Eye Irritation:  0.507 Respiratory Toxicity:  0.895
Drug-induced Neurotoxicity:  0.154 Ototoxicity:  0.825
Hematotoxicity:  0.791 Drug-induced Nephrotoxicity:  0.947
Genotoxicity:  0.879 RPMI-8226 Immunitoxicity:  0.218
A549 Cytotoxicity:  0.324 Hek293 Cytotoxicity:  0.362
BCF:   0.396
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   3.104
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.768
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.831
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO18028 Isodon scoparius Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[19072209]
NPO18028 Isodon scoparius Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[28654256]
NPO20759 Isodon inflexa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18028 Isodon scoparius Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20759 Isodon inflexa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20759 Isodon inflexa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18028 Isodon scoparius Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2678 Cell line NB-4 Homo sapiens IC50 > 10000.0 nM PMID[19072209]
NPT81 Cell line A549 Homo sapiens IC50 > 10000.0 nM PMID[19072209]
NPT519 Cell line SH-SY5Y Homo sapiens IC50 > 10000.0 nM PMID[19072209]
NPT306 Cell line PC-3 Homo sapiens IC50 > 10000.0 nM PMID[19072209]
NPT83 Cell line MCF7 Homo sapiens IC50 > 10000.0 nM PMID[19072209]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC138245 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.7234 Intermediate Similarity NPC181594
0.6875 Remote Similarity NPC59170
0.66 Remote Similarity NPC84018
0.6531 Remote Similarity NPC191094
0.6327 Remote Similarity NPC101233
0.6078 Remote Similarity NPC231060
0.6078 Remote Similarity NPC16164
0.6 Remote Similarity NPC87927
0.5962 Remote Similarity NPC144739
0.5962 Remote Similarity NPC29112
0.5818 Remote Similarity NPC148628
0.5769 Remote Similarity NPC291785
0.5686 Remote Similarity NPC261994
0.5686 Remote Similarity NPC470378
0.5636 Remote Similarity NPC132813
0.5636 Remote Similarity NPC147965
0.5536 Remote Similarity NPC52899
0.5536 Remote Similarity NPC327247
0.5472 Remote Similarity NPC179399
0.5283 Remote Similarity NPC165895
0.5192 Remote Similarity NPC111524
0.5185 Remote Similarity NPC261333
0.5172 Remote Similarity NPC163963
0.5094 Remote Similarity NPC153775
0.5094 Remote Similarity NPC289539

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC138245 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data